In mass spectrometry that is an important method of analysis in organic chemistry, in general, an object substance is ionized in some method and the ion is desorbed and detected in a TOF apparatus using the difference of flight time between ions based on the difference in mass-to-charge ratio (m/z). It is known that a sample to be analyzed may be soft-ionized not requiring decomposition of the molecules thereof in MALDI mass spectrometry in which the sample is mixed with an organic low-molecular ionization assistant (matrix agent) and locally irradiated with laser (e.g., 337 nm), whereby the matrix agent absorbs the laser beam to cause rapid temperature elevation in only the irradiated site. The method is widely utilized as a means for analyzing compounds such as protein, synthetic polymer and the like in the field of medicine, clinical medicine, food, polymer material and environment.
The matrix for use in MALDI mass spectrometry (in this description, this may be referred to as “laser-light-absorbing matrix”) may be roughly grouped into the following types:    (a) Organic matrix having a double bond or an aromatic ring as a functional group,    (b) Inorganic matrix comprising inorganic fine particles.
In the method of using the above-mentioned organic matrix (a), it is important to investigate the optimum condition (type of the organic matrix and the solvent to be added to sample, their blend ratio, crystal state of the mixed crystal of sample and matrix) for every sample prior to analysis thereof. Naturally, the chemical reaction between the organic matrix and the organic compound sample may bring about some problems. In particular, the reaction in laser irradiation must be taken into consideration. The organic matrix itself is ionized and decomposed through laser irradiation, therefore producing many interfering ion peaks resulting from it. Accordingly, MALDI mass spectrometry using an organic matrix has an essential problem in that an organic compound having a relatively small molecular weight is especially difficult to analyze therein.
As the method of using the inorganic matrix of fine particles of the above (b), known is a method of mixing a suspension of inorganic fine particles (e.g., Co fine particles) coated with a high-viscosity liquid such as glycerin or the like, with a sample substance (Patent Reference 1). When inorganic fine particles are used directly as they are, then, in general, sample molecules may be strongly adsorbed by the inorganic fine particles (multipoint adsorption), and therefore the sample molecules could hardly be desorbed in laser irradiation and accurate mass spectrometry may be difficult. Inorganic fine particles of transition metals except some noble metals may be readily oxidized in air and their surface conditions often change, and therefore it is difficult to apply them to mass spectrometry directly as they are. In this connection, according to the above-mentioned method of coating with a high-viscosity liquid such as glycerin or the like, sample molecules may float in the high-viscosity liquid that covers the inorganic fine particles, and the sample molecules ionized through laser irradiation can be readily desorbed from the matrix. In addition, since the high-viscosity liquid could serve as a protective agent, aerial oxidation in the case of using metal fine particles may be prevented. However, in a mass spectrometer, the ion source part is in high vacuum, therefore causing a problem of apparatus contamination with the protective agent such as glycerin or the like. Accordingly, at present, the method is not almost used.
Also proposed is a method of forming a functional group in the surface of silica particles through surface treatment and using the particles as a matrix (Patent Reference 2). However, the method requires preparation of suitable surface treatment according to the sample substance to be analyzed, and the operation is complicated. In addition, the substance adhered by the surface treatment may cause interfering ion peaks.
In addition, other some metal nanoparticles are proposed as a matrix; however, the reducing agent to be added in producing metal nanoparticles and the surface-protective agent for nanoparticles often cause interfering ion peaks, and therefore analysis of low-molecular-weight organic compounds is still difficult.
On the other hand, also known is a DIOS method of using a porous surface substrate having a fine pore structure of several tens nm, as one utilizing the substrate itself on which a sample substance is put, as a laser-beam-absorbing ionization medium (Non-Patent Reference 1). Above all, the DIOS method of using porous silicon has been already put into practical use, which suffers from few interfering ion peaks derived from the laser-beam-absorbing ionization medium in the region of analyzing substances having a molecular weight of not larger than 1000. However, this still has a problem of durability in that the silicon surface is readily oxidized in air and the ionization efficiency is thereby greatly lowered.
Further, it is said that, in the DIOS method, sample substrates having the same porous structure are difficult to produce with good reproducibility, and in addition, a problem is pointed out in that the method is not so much suitable for repeated measurement since washing the porous substrate once used for measurement is not easy. Accordingly, in Patent Reference 3, solving the problems with the DIOS method is tried by using a crystalline element having the property of absorbing laser beams at high efficiency (pyro-electric element having a property of spontaneous polarization based on the temperature changes, and ferroelectric element) as a sample substrate. However, the method indispensably requires preparation of a special sample substrate, in which, therefore, commercially-available sample substrates for MALDI mass spectrometry (SiC substrate, etc.) could not be used. Accordingly, at present, the method lacks popularity and the cost in measurement is high.
Patent Reference 1: JP-A 62-43562
Patent Reference 2: JP-T 2005-502050
Patent Reference 3: JP-A 2006-201042
Non-Patent Reference 1: Wei, J., Buriak, J. M., Siuzdak, G.; Nature 1999, 399, 243-6